Probing neural circuits underlying satiety

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

We seek to elucidate the neural circuit mechanisms governing satiety and meal termination, processes that are fundamental to energy balance and metabolic homeostasis. Our group applies state-of-the-art circuit interrogation tools—including optogenetics, chemogenetics, and in vivo calcium imaging—to dissect how hypothalamic neurons interface with brainstem nuclei and thalamic hubs to constrain feeding. This work addresses a core area of the NIH mission by probing how disruptions in central control of feeding contribute to obesity, type 2 diabetes, and metabolic syndrome. A central programmatic emphasis of the Krashes laboratory is to define the integration of peripheral nutrient and hormonal feedback with central satiety pathways, situating our work at the interface of neuroscience, endocrinology, and metabolism. Our research examines how gut-derived signals (e.g., cholecystokinin, GLP-1, and amylin) modulate hypothalamic and brainstem satiety neurons to terminate ongoing food intake, and how these signals are processed in mesolimbic reward systems to suppress motivational drive. This research directly contributes to NIH-supported initiatives in obesity biology, metabolic disease mechanisms, and gut-brain axis signaling, aligning with goals to understand the physiological basis of appetite regulation. The Krashes program further extends into systems neuroscience of motivational state integration, investigating how satiety signals are overridden or attenuated by competing drives such as thirst, stress, or the rewarding properties of palatable food. By identifying the molecular and circuit-level nodes that balance hunger and satiety, this work provides mechanistic insight into why satiety control often fails in obesity, binge eating disorder, and related psychiatric conditions. Collectively, these studies advance NIH priorities in understanding brain-body communication, promoting healthy weight, and developing novel therapeutic strategies to strengthen satiety responses and restore adaptive feeding behavior in metabolic disease.